The proposed competitive renewal of our grant, Bone Strength Through the Menopausal Transition: Trabecular Bone Score, builds upon the Study of Women's Health Across the Nation (SWAN) Bone Project. SWAN is a multi-site, multi-racial/ethnic longitudinal study designed to characterize the physiological and psychosocial changes that occur during the menopausal transition (MT). One of the key physiological consequences of ovarian aging that was specifically targeted in SWAN was loss in skeletal mass. In SWAN, areal bone mineral density (aBMD) loss begins 2 years before the final menstrual period (FMP) at both the lumbar spine (LS) and femoral neck (FN) sites. Cumulative rates of bone loss are greatest from 1 year before through 2 years after the FMP, termed the transmenopause. Bone loss 2-5 years after the FMP slows. Germane to this application, transmenopausal BMD loss is greater at the LS than at FN, concordant with the higher proportion of trabecular bone in the LS. We also found that LS, but not FN, aBMD was associated with incident fractures across the MT, again emphasizing the potential dominant role of trabecular bone. However, in SWAN we are currently limited to dual-energy x-ray absorptiometry (DXA) measures of aBMD which cannot distinguish trabecular and cortical bone. The trabecular bone score (TBS) is a new index of trabecular bone structure that can be obtained from LS DXA scans. Microarchitecture of trabecular bone is a key determinant of bone strength. Both thinning of trabeculae and loss of trabecular connectivity substantially undermines structural integrity and weakens bone. TBS is associated with other measures of trabecular bone structure and predicts fracture in postmenopausal women. Our proposal offers an unprecedented cost-efficient opportunity to investigate trabecular bone structure longitudinally in the SWAN cohort. No other study has LS aBMD serially for a 20- year time span that includes the entire MT in a large multiracial sample. By reanalyzing SWAN spine DXA scans to obtain TBS we have the unique opportunity to isolate trabecular microarchitecture and test several novel hypotheses. The specific aims of our study are to: (1)Determine the direction and magnitude of ethnic difference in TBS at baseline when all participants were either premenopausal or early perimenopausal and so at or near their peak BMD. (2)Examine the rate of longitudinal change in TBS with aging and with the MT (3) Examine the association between baseline TBS and incident fractures in midlife women. (4)Examine the effect of diabetes and insulin resistance on TBS at baseline and longitudinally as women traverse the MT. The central tenet of our work is beyond aBMD. This proposal builds on our initial grant where we made sub- stantial contributions showing that hip structural, biomechanical and geometric elements improves risk class- ification. We now propose to focus on LS trabecular microarchitecture and test whether the rapid trans- menopausal loss preferentially effects trabecular bone which could lead to irreparable structure damage. Our long term objective is to substantially improve our understanding of aging, menopause and skeletal strength.